LC/MS/MS for identification of in vivo and in vitro metabolites of jatrorrhizine

Abstract

The in vivo and in vitro metabolism of jatrorrhizine has been investigated using a specific and sensitive LC/MS/MS method. In vivo samples including rat feces, urine and plasma collected separately after dosing healthy rats with jatrorrhizine (34 mg/kg) orally, along with in vitro samples prepared by incubating jatrorrhizine with rat intestinal flora and liver microsome, respectively, were purified using a C(18) solid-phase extraction cartridge. The purified samples were then separated with a reversed-phase C(18) column with methanol-formic acid aqueous solution (70:30, v/v, pH3.5) as mobile phase and detected by on-line MS/MS. The structural elucidation of the metabolites was performed by comparing their molecular weights and product ions with those of the parent drug. As a result, seven new metabolites were found in rat urine, 13 metabolites were detected in rat feces, 11 metabolites were detected in rat plasma, 17 metabolites were identified in intestinal flora incubation solution and nine metabolites were detected in liver microsome incubation solution. The main biotransformation reactions of jatrorrhizine were the hydroxylation reaction, the methylation reaction, the demethylation reaction and the dehydrogenation reaction of parent drug and its relative metabolites. All the results were reported for the first time, except for some of the metabolites in rat urine.

Pharmacokinetics and metabolism of jatrorrhizine, a gastric prokinetic drug candidate

“…The number of jatrorrhizine metabolites detected in the present study was less than that in previous reports . However, the metabolism reported in the present study showed a better correlation with the actual application of jatrorrhizine in rats because the dosage used (3 mg/kg) can effectively improve gastric motility.…”

“…34 mg/kg or i.v. 12 mg/kg in rats) . Moreover, a sulfated product of jatrorrhizine (sulfated jatrorrhizine) was detected, and the demethylation position on the jatrorrhizine molecule was confirmed.…”

“…Therefore, a metabolic pathway for the conversion of jatrorrhizine could be considered as an important elimination pathway. Although several reports on the metabolites of jatrorrhizine in rats have been published , very little is known about its metabolic characterization. The present investigation reveals the metabolic characterization of major jatrorrhizine metabolites, including their kinetic profiles, key CYPs and UGTs.…”

“…After intragastric (i.g.) administration of jatrorrhizine at 34 mg/kg weight, 13 metabolites were detected in rat feces, 11 in rat plasma, 17 in intestinal flora incubation solution and nine in rat liver microsomes (RLMs) . However, the dosages in these studies were quite high.…”

Compound to Extract to Formulation: a knowledge-transmitting approach for metabolites identification of Gegen-Qinlian Decoction, a traditional Chinese medicine formula

“…Their distribution and metabolism had been reported in several different organisms3233343536. We chose palmatine ( C1 ) and berberine ( C2 ) for metabolic studies.…”